Our current research involves mammary tumor growth and differentiation. One aspect of this has centered on a unique ribonuclease we discovered in rat mammary gland, milk and hormone sensitive mammary tumors. On pondering the function of this enzyme, our studies led us to a possible link with the 2,5An (an oligoadenylate with 2 feet, 5 feet-linkage: ppp(2 feet p5 feet A)n, designated here simly as 2,5An) system induced by interferon. Early work, however, revealed an even more interesting facet of this system, that of its own relationship to cell growth and differentiation. We wish to continue our investigations to enhance our studies by determining if the 2,5An system plays a role in the regulation of mammary tumor growth. One of the suspected mechanisms of interferon's antiviral and antimitogenic activities involves the induction of 2,5An synthesis. However, many different cells not exposed to a virus or interferon contain enzymes that synthesize and degrade 2,5An. We observed 2,5An synthesis in normal rat liver nuclei, but it was absent from cytosol, the site where 2,5An triggers a cascade of biochemical reactions. Furthermore, nuclear 2,5An synthesis was diminished by partial hepatectomy. 2,5An synthesis also occurs in nuclei from lactating rat mammary gland which also is comprised mostly of differentiated cells that have ceased to divide. These results suggest the actions of 2,5An are inversely related to mitotic activity. Changes in 2,5An synthetase/2 feet-phosphodiesterase and 2,5An will be determined in the mammary gland during growth and differentiation and in tumors under various growth conditions caused by hormonal or drug treatments. These changes will be compared with the changes in DNA synthesis or cell replication. Also mechanisms of 2,5An action associated with cell replication will be investigated. The results will define 2,5An's role in cell growth and differentiation, provide a better understanding of tumor regulation and have possible therapeutic importance.